The c-Jun amino terminal kinase (JNK) is a member of the stress-activated group of mitogen-activated protein (MAP) kinases. The JNK signal transduction pathway is activated in response to environmental stress and by several classes of cell surface receptors, such as for example, cytokine receptors, serpentine receptors, and receptor tyrosine kinases. JNK is activated by dual phosporylation that is mediated by a protein kinase cascade that consists of a MAP kinase (MAPK), a MAP kinase kinase (MAPKK), and a MAP kinase kinase kinase (MAPKKK). Targets of the JNK signaling pathway include transcriptions factors, such as for example, the transcription factors ATF2 and c-Jun.
These kinases have been implicated in the control of cell growth and differentiation, and, more generally, in the response of cells to environmental stimuli. In mammalian cells, JNK has been implicated in such biological processes as oncogenic transformation and in mediating adaptive responses to environmental stress. JNK has also been associated with modulating immune responses, including maturation and differentiation of immune cells, as well effecting programmed cell death in cells identified for destruction by the immune system.
Studies have implicated the JNK signaling pathway in apoptosis and survival signaling, and in particular, JNK has been recognized as a component of the stress-induced apoptotic signaling mechanism. Studies have shown that JNK is required for the stress-induced release of mitochondrial cytochrome c, and therefore, JNK is required for stress-induced apoptosis that is mediated by the mitochondrial/caspase-9 pathway.